Dependence of human platelet functional responses on divalent cations: aggregation and secretion in heparin- and hirudin-anticoagulated platelet-rich plasma and the effects of chelating agents.
The dependence of ADP- and epinephrine-induced platelet aggregation and secretion on extracellular divalent cations was examined by quantitating these responses in citrate-, heparin-, and hirudin-anticoagulated platelet-rich plasma. ADP-induced 14C-5HT secretion in heparin-PRP and hirudin-PRP was generally decreased, relative to that in citrate-PRP, without corresponding reductions in aggregation, whereas in response to epinephrine, both aggregation and secretion were decreased in heparin-PRP, and abolished in hirudin-PRP. In heparin-PRP, but not in hirudin-PRP, the degree to which these responses were altered was highly variable among normal subjects, and was dependent on the anticoagulant concentration. Addition of citrate restored the extent of ADP-induced secretion and of epinephrine-induced aggregation and secretion in heparin-PRP to that observed in citrate-PRP, and increased the extent of ADP-induced secretion in hirudin-PRP. Addition of EDTA or EGTA, however, had no effect of ADP-induced secretion in heparin-PRP. These results suggest that ADP-induced aggregation and secretion, as well as responses to ADP vs. epinephrine, have different dependencies on extracellular or surface-bound divalent cations. The variable responses observed in heparin-PRP may reflect direct interactions of heparin with platelets, and this variability may account for the conflicting results of previous studies.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000097:blood; D002413:Cations, Divalent; D002614:Chelating Agents / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D006801:Humans; D008274:Magnesium / Q000097:blood; D010974:Platelet Aggregation
D000925:Anticoagulants; D002413:Cations, Divalent; D002614:Chelating Agents; D002951:Citrates; D006629:Hirudins; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D006493:Heparin; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium; D004837:Epinephrine